AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 38-L44, Copyright © 1995 by American Physiological Society
Bradykinin stimulates bronchial epithelial cells to release neutrophil and monocyte chemotactic activity
S. Koyama, S. I. Rennard and R. A. Robbins
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
In the present investigation, we evaluated the potential of bradykinin
(BK), histamine, and serotonin to induce the release of neutrophil and
monocyte chemotactic activity (NCA and MCA) from bronchial epithelial cells
(BEC). BK significantly stimulated BEC to release NCA and MCA in a dose-
and time-dependent manner. Histamine weakly but significantly induced the
release of both NCA and MCA in a similar fashion. Serotonin did not
stimulate BEC. Checkerboard analysis showed that the NCA and MCA released
in response to BK were chemotactic. Molecular-sieve column chromatography
by Sephadex G-75 revealed that BK induced a single low-molecular-weight
peak (approximately 400 Da) for both NCA and MCA. The releases of NCA and
MCA in response to BK and histamine were inhibited by lipoxygenase
inhibitors (P < 0.01). The released NCA was inhibited by leukotriene B4
(LTB4) receptor antagonist (P < 0.01) and was slightly inhibited by
platelet-activating factor receptor antagonist. LTB4 was increased in
BK-stimulated BEC supernatant (P < 0.01). BK B2-receptor antagonist
attenuated the release of NCA and MCA. These data suggest that BK and
histamine may stimulate BEC to release NCA and MCA and may modulate
neutrophil and monocyte recruitment into the airways in patients with
asthma.
